Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background: Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine. Methods: This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11-17 years for OSCC (mean 13.3), 12-22 years for OLP (mean 15.9) and 12-17 years for hyperkeratosis (mean 14.5). Results: Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 (n = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53-mutated out of 31 tested. One TP53-mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site. Conclusion: TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.